LDDRD has established an active network of collaborations aimed at structure-activity investigations and lead optimization research within selected series of novel antitumor and anti-HIV natural products. The goal is to introduce into the NCI drug development program improved members of known chemical and/or mechanistic classes currently under development and of continuing interest, as well as to introduce the best representatives of entirely new active chemical and/or mechanistic classes for consideration for entry into the drug development program. Subjects of current chemical and biological investigations include halichondrin-related compounds, dolastatins, cephalostatins, cribrostatins, michellamine derivatives, calanolide derivatives and related compounds, ellipticines, ellipticiniums and related agents.